The Mass Spectrometry metabolomics core has well established methodologies to provide qualitative and quantitative measures of specific metabolites such as amino acids, lipid-related metabolites including ceramides, phosphometabolites, and substrates of the citric acid cycle as well as drug metabolites. These measurements complement our methodologies to measure stable isotope abundance in a variety of molecules including fatty acids, amino acids, carbohydrates, and phosphometabolites. These methodologies in combination with our expertise in multi-compartment modeling offer the opportunity to not only to measure the concentrations of metabolites but also to understand how concentrations are determined by changes in the rate of appearance or disposal of a given analyte. It also allows us to determine the metabolic fates and dynamics of the metabolic network of various metabolic processes between various body compartments. The current facility has 11 different classes of mass spectrometer supported by 9 highly trained technical staff and supports over 50 investigators (40 of whom are NIH-funded). Currently < 10% of the services undertaken are provided to investigators outside Mayo Clinic. The mass spectrometry Core is closely integrated to the NMRS core to complement our mutual strengths and is connected closely with the proteomics, genomics and microbiome programs which are all served by a common bioinformatics/bio statistics group. There are multiple requests for access to our facility from investigators from other national centers but only an expanded facility can respond to the increasing demands. In this application we propose the acquisition of three additional mass spectrometers and three additional technical staff so as to expand the analytical capabilities as well as the overall capacity of the core enabling an expansion of the services provided to a larger number of investigators both within and outside of the Mayo Clinic. The existing facilities currently provide assistance to investigators in isotope selection and experimental design as well as bioinformatics and mathematical modeling support thereby enabling the research objectives to be accomplished. The plan is to enable the program to be self-sustaining within a five year period. We have an established prioritization program for sample analysis that was approved by NIH review at the time of our CTSA grant renewal and that program will be extended to meet the requirement of the proposed comprehensive program. Thus the overall goal of this application is to expand the facility enabling us to offer the expertise and services to other national institutions thereby advancing metabolomics-based